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EDIBLE VACCINES
K SUDHEER KUMAR
Associate Professor
MAK COLLEGE OF PHARMACY , HYD.
Sudheer.y2k8@gmail.com
A vaccine is a biological preparation that improves immunity to a
particular disease.
It contains an agent that resembles a disease-causing microorganism
and is often made from weakened or killed forms of the microbe, its
toxins or one of its surface proteins.
The agent stimulates the body's immune system to recognize the
foreign antigen, destroy it.
Edward Jenner (1796) used this vaccine in human beings resulting in
protection of human beings from smallpox. Jenner's work was
continued by Louis Pasteur .
Vaccines can be
PROPHYLACTIC (e.g. to prevent the effects of a future infection by
any natural or "wild" pathogen)
THERAPEUTIC (e.g. vaccines against cancer )
Ideal vaccine
It should not be toxic or pathogenic.
Low levels of side effect.
It should not contaminate the environment.
It should not cause problems in individual.
Technique of vaccination should be simple.
It should be cheap.
In the edible vaccine, Transgenic plants are used as vaccine
production systems.
The genes encoding antigens of bacterial and viral pathogens can
be expressed in plants in a form in which they retain native
immunogenic properties.
Initially thought to be useful only for preventing infectious
diseases, it has also found application in prevention of
autoimmune diseases, birth control , cancer therapy, etc.
Edible vaccines are currently being developed for a number of
human and animal diseases.
As Hippocrates said , Let “the food be the medicine”
Method of Developing an Edible Vaccine
Gene encoding antigen from pathogenic organisms (virus,
bacteria or parasites) that have been characterized and for
which antibodies are available, can be produced in the edible
parts of the plants in two ways.
In one case, the entire structural gene is inserted into a plant
transformation vector.
This will allow transcription and accumulation of coding
sequence in plant.
In second case, epitope within the antigen are identified, DNA
fragment encoding these can be used to construct genes by fusion
with a coat protein gene from plant virus, e.g., TMV (Tobacco
mosaic virus) or CMV (Cytomegalovirus) .
The recombinant virus is then used to infect stabilized plants. The
resultant edible plant vaccines are utilized for further
immunological studies.
Candidates for Edible Vaccines
Foods under study of edible vaccines include bananas, potatoes
and tomatoes as well as lettuce, rice, wheat, soybean and corn.
When choosing a plant to be used as a vaccine it is important
that it is a hardy, palatable plant with high nutritive and protein
content.
The plant is also one that would best be indigenous to the
country in which it is to be used and should be able to be
transformed with relative ease.
1. Tobacco
2. Potato
3. Banana
4. Tomato
5. Rice
6. Lettuce
7. Soybean
8. Alfalfa
9. Muskmelon
10. Carrot
11. Peanuts
12. Wheat
13. Corn
PLANTS USED FOR EDIBLE VACCINS
MECHANISM OF ACTION
The goal of oral vaccination is to stimulate the mucosal and systemic immunity
against pathogen.
Edible vaccine when taken orally undergoes the mastication process and the
majority of plant cell degradation occur in the intestine as a result of action of
digestive or bacterial enzyme on edible vaccine .
Peyer‟s patches (PP) small masses of lymphatic tissue found throughout the
ileum region of the small intestine. Monitor intestinal bacteria populations
and preventing the growth of pathogenic bacteria in the intestines. are an
enriched source of IgA producing plasma cells and have the potential to
populate mucosal tissue and serves as mucosal immune effector site.
The breakdown of edible vaccine near PP , consisting of the 30-40
lymphoid nodules on the outer surface of intestine and contain follicles.
These follicles act as the site from which antigen penetrates the
intestinal epithelium ,thereby accumulating antigen within organized
lymphoid structure .
The antigen then comes in contact with M-cell .
M cell passes the antigen to macrophages and B cell.
These B cell activates the T cell to provide immune response .
In this way the immunity is activated by the edible vaccine.
Norwalk virus (causes viral gastroenteritis, which is also known as acute
nonbacterial gastroenteritis, food poisoning, food infection, stomach flu,
and winter vomiting disease)
Transgenic potato expressing norwalk virus antigen showed
seroconversion.
Nineteen (95%) out of 20 people fed with transgenic potato
expressing norwalk virus antigen showed seroconversion .
 Attempts are underway to engineer bananas and powdered
tomatoes expressing norwalk virus.
Cholera (Cholera is an infectious disease that causes severe watery
diarrhea, which can lead to dehydration and even death if untreated. It is
caused by eating food or drinking water contaminated with a bacterium
called Vibrio cholerae)
Transgenic potato with CT-B gene of Vibrio cholerae was shown
to be effective in mice.
Eating one potato a week for a month with periodic boosters
was said to provide immunity.
Measles ( Measles is an infectious disease caused by the rubeola virus)
Mice fed with tobacco expressing MV-H could attain antibody titers
five times the level considered protective for humans.
 MV-H edible vaccine does not cause atypical measles, which may be
occasionally seen with the current vaccine.
Transgenic rice, lettuce and baby food against measles are also being
developed.
Hepatitis B infection of your liver. It can cause
scarring of the organ, liver failure, and cancer.
First human trials of a potato based vaccine
against hepatitis B have reported
The amount of HBsAg needed for one dose
could be achieved in a single potato.
When cloned into CaMv , plasmid HBsAg
subtype showed higher expression in roots as
compared to leaf tissue of the transgenic
potato.
NEWCASTLE DISEASE (contagious viral bird disease)
NDV is highly infectious, affecting domestic poultry and wild birds.
NDV transmission occurs through direct contact with secretions or
discharge of infected birds, and contact with fomites.
The world‟s first regulatory approval for a PMV (Panicum mosaic virus)
was against NDV.
The HN protein from NDV was expressed in a tobacco cell system and
found to retain the size and immuno reactivity.
FOOT-AND-MOUTH DISEASE
Foot-and-mouth disease (FMD) is one of the most contagious viral
diseases of wild ruminant and domestic animals.
The causative pathogen, FMD virus (FMDV).
FMDV is a single-stranded, positive-sense RNA virus, possessing four
capsid proteins VP1 , VP2 , VP3 and VP4 .
The VP1 protein is the critical determinant for vaccination against FMD
with the induction of VP1-neutralizing antibodies required for
immunity.
Studies have shown the potential of using VP1 capsid protein as a
subunit PMV candidate, in potato, tobacco, and tomato.
AVIAN INFLUENZA (Bird flu)
There are three influenza viral types A, B and C with distinct
pathogenicity and genome properties.
Influenza type A virus is endemic in aquatic birds. It is contagious not
only to avian species but also to a variety of mammals.
Influenza types B and C infect mainly humans and are generally less
lethal.
High accumulation of VLPs made antigen was observed to be
immunogenic.
Mice immunized intramuscularly with doses of purified VLPs were
protected against influenza virus.
Advantages of Edible Vaccines
Edible means of administration. Reduced need for medical personnel
and sterile injection conditions. Economical in mass production and trans-
portation.
Therapeutic proteins are free of pathogens and toxins. Storage near the
site of use.
Heat stable, eliminating the need for refrigeration. Antigen protection
through bio-encapsulation.
Subunit vaccine (not attenuated pathogens) means improved safety.
Generation of systemic and mucosal immunity.
Enhanced compliance (especially in children).Delivery of multiple
antigens. Plant derived antigens assemble spontaneously into oligomers
and into virus like particles
Limitations of Edible Vaccines
a. Development of immuno tolerance to vaccine peptide or protein.
b. Consistency of dosage form fruit to fruit, plant to plant, and
generation-to-generation is not similar.
c. Stability of vaccine in fruit is not known.
d. Evaluating dosage requirement is tedious.
e. Selection of best plant is difficult.
f. Certain foods like potato are not eaten raw, and cooking the food
might weaken the medicine present in it.
Regulatory Issues
It is still unclear whether the edible vaccines would be regulated under food,
drugs or agricultural products and what vaccine component would be licensed
- antigen itself, genetically engineered fruit or transgenic seeds.
They would be subjected to a very close scrutiny by the regulatory bodies in
order to ensure that they never enter the food supply.
This would include greenhouse segregation of medicinal plants from food
crops to prevent out-crossing and would necessitate separate storage and
processing facilities.
Although edible vaccines fall under "GM" plants, it is hoped that these
vaccines will avoid serious controversy, because they are intended to save
lives.
Whatever may be the current situation, a day is not far off when we
will be able to pluck a fruit from the garden, eat it and be protected
from diseases…making needles needless…

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EDIBLE VACCINES

  • 1. EDIBLE VACCINES K SUDHEER KUMAR Associate Professor MAK COLLEGE OF PHARMACY , HYD. Sudheer.y2k8@gmail.com
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  • 3. A vaccine is a biological preparation that improves immunity to a particular disease. It contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body's immune system to recognize the foreign antigen, destroy it. Edward Jenner (1796) used this vaccine in human beings resulting in protection of human beings from smallpox. Jenner's work was continued by Louis Pasteur .
  • 4. Vaccines can be PROPHYLACTIC (e.g. to prevent the effects of a future infection by any natural or "wild" pathogen) THERAPEUTIC (e.g. vaccines against cancer ) Ideal vaccine It should not be toxic or pathogenic. Low levels of side effect. It should not contaminate the environment. It should not cause problems in individual. Technique of vaccination should be simple. It should be cheap.
  • 5. In the edible vaccine, Transgenic plants are used as vaccine production systems. The genes encoding antigens of bacterial and viral pathogens can be expressed in plants in a form in which they retain native immunogenic properties. Initially thought to be useful only for preventing infectious diseases, it has also found application in prevention of autoimmune diseases, birth control , cancer therapy, etc. Edible vaccines are currently being developed for a number of human and animal diseases. As Hippocrates said , Let “the food be the medicine”
  • 6. Method of Developing an Edible Vaccine Gene encoding antigen from pathogenic organisms (virus, bacteria or parasites) that have been characterized and for which antibodies are available, can be produced in the edible parts of the plants in two ways. In one case, the entire structural gene is inserted into a plant transformation vector. This will allow transcription and accumulation of coding sequence in plant.
  • 7. In second case, epitope within the antigen are identified, DNA fragment encoding these can be used to construct genes by fusion with a coat protein gene from plant virus, e.g., TMV (Tobacco mosaic virus) or CMV (Cytomegalovirus) . The recombinant virus is then used to infect stabilized plants. The resultant edible plant vaccines are utilized for further immunological studies.
  • 8. Candidates for Edible Vaccines Foods under study of edible vaccines include bananas, potatoes and tomatoes as well as lettuce, rice, wheat, soybean and corn. When choosing a plant to be used as a vaccine it is important that it is a hardy, palatable plant with high nutritive and protein content. The plant is also one that would best be indigenous to the country in which it is to be used and should be able to be transformed with relative ease.
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  • 11. 1. Tobacco 2. Potato 3. Banana 4. Tomato 5. Rice 6. Lettuce 7. Soybean 8. Alfalfa 9. Muskmelon 10. Carrot 11. Peanuts 12. Wheat 13. Corn PLANTS USED FOR EDIBLE VACCINS
  • 12. MECHANISM OF ACTION The goal of oral vaccination is to stimulate the mucosal and systemic immunity against pathogen. Edible vaccine when taken orally undergoes the mastication process and the majority of plant cell degradation occur in the intestine as a result of action of digestive or bacterial enzyme on edible vaccine . Peyer‟s patches (PP) small masses of lymphatic tissue found throughout the ileum region of the small intestine. Monitor intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestines. are an enriched source of IgA producing plasma cells and have the potential to populate mucosal tissue and serves as mucosal immune effector site.
  • 13. The breakdown of edible vaccine near PP , consisting of the 30-40 lymphoid nodules on the outer surface of intestine and contain follicles. These follicles act as the site from which antigen penetrates the intestinal epithelium ,thereby accumulating antigen within organized lymphoid structure . The antigen then comes in contact with M-cell . M cell passes the antigen to macrophages and B cell. These B cell activates the T cell to provide immune response . In this way the immunity is activated by the edible vaccine.
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  • 17. Norwalk virus (causes viral gastroenteritis, which is also known as acute nonbacterial gastroenteritis, food poisoning, food infection, stomach flu, and winter vomiting disease) Transgenic potato expressing norwalk virus antigen showed seroconversion. Nineteen (95%) out of 20 people fed with transgenic potato expressing norwalk virus antigen showed seroconversion .  Attempts are underway to engineer bananas and powdered tomatoes expressing norwalk virus.
  • 18. Cholera (Cholera is an infectious disease that causes severe watery diarrhea, which can lead to dehydration and even death if untreated. It is caused by eating food or drinking water contaminated with a bacterium called Vibrio cholerae) Transgenic potato with CT-B gene of Vibrio cholerae was shown to be effective in mice. Eating one potato a week for a month with periodic boosters was said to provide immunity.
  • 19. Measles ( Measles is an infectious disease caused by the rubeola virus) Mice fed with tobacco expressing MV-H could attain antibody titers five times the level considered protective for humans.  MV-H edible vaccine does not cause atypical measles, which may be occasionally seen with the current vaccine. Transgenic rice, lettuce and baby food against measles are also being developed.
  • 20. Hepatitis B infection of your liver. It can cause scarring of the organ, liver failure, and cancer. First human trials of a potato based vaccine against hepatitis B have reported The amount of HBsAg needed for one dose could be achieved in a single potato. When cloned into CaMv , plasmid HBsAg subtype showed higher expression in roots as compared to leaf tissue of the transgenic potato.
  • 21. NEWCASTLE DISEASE (contagious viral bird disease) NDV is highly infectious, affecting domestic poultry and wild birds. NDV transmission occurs through direct contact with secretions or discharge of infected birds, and contact with fomites. The world‟s first regulatory approval for a PMV (Panicum mosaic virus) was against NDV. The HN protein from NDV was expressed in a tobacco cell system and found to retain the size and immuno reactivity.
  • 22. FOOT-AND-MOUTH DISEASE Foot-and-mouth disease (FMD) is one of the most contagious viral diseases of wild ruminant and domestic animals. The causative pathogen, FMD virus (FMDV). FMDV is a single-stranded, positive-sense RNA virus, possessing four capsid proteins VP1 , VP2 , VP3 and VP4 . The VP1 protein is the critical determinant for vaccination against FMD with the induction of VP1-neutralizing antibodies required for immunity. Studies have shown the potential of using VP1 capsid protein as a subunit PMV candidate, in potato, tobacco, and tomato.
  • 23. AVIAN INFLUENZA (Bird flu) There are three influenza viral types A, B and C with distinct pathogenicity and genome properties. Influenza type A virus is endemic in aquatic birds. It is contagious not only to avian species but also to a variety of mammals. Influenza types B and C infect mainly humans and are generally less lethal. High accumulation of VLPs made antigen was observed to be immunogenic. Mice immunized intramuscularly with doses of purified VLPs were protected against influenza virus.
  • 24. Advantages of Edible Vaccines Edible means of administration. Reduced need for medical personnel and sterile injection conditions. Economical in mass production and trans- portation. Therapeutic proteins are free of pathogens and toxins. Storage near the site of use. Heat stable, eliminating the need for refrigeration. Antigen protection through bio-encapsulation. Subunit vaccine (not attenuated pathogens) means improved safety. Generation of systemic and mucosal immunity. Enhanced compliance (especially in children).Delivery of multiple antigens. Plant derived antigens assemble spontaneously into oligomers and into virus like particles
  • 25. Limitations of Edible Vaccines a. Development of immuno tolerance to vaccine peptide or protein. b. Consistency of dosage form fruit to fruit, plant to plant, and generation-to-generation is not similar. c. Stability of vaccine in fruit is not known. d. Evaluating dosage requirement is tedious. e. Selection of best plant is difficult. f. Certain foods like potato are not eaten raw, and cooking the food might weaken the medicine present in it.
  • 26. Regulatory Issues It is still unclear whether the edible vaccines would be regulated under food, drugs or agricultural products and what vaccine component would be licensed - antigen itself, genetically engineered fruit or transgenic seeds. They would be subjected to a very close scrutiny by the regulatory bodies in order to ensure that they never enter the food supply. This would include greenhouse segregation of medicinal plants from food crops to prevent out-crossing and would necessitate separate storage and processing facilities. Although edible vaccines fall under "GM" plants, it is hoped that these vaccines will avoid serious controversy, because they are intended to save lives.
  • 27. Whatever may be the current situation, a day is not far off when we will be able to pluck a fruit from the garden, eat it and be protected from diseases…making needles needless…